Alterations in Gamma-Delta T Cells in Patients With Primary Biliary Cholangitis

Background & Aims Gamma-delta (γδ) T cells are involved in the development of diverse liver and autoimmune diseases, whereas the role of γδ T cells in primary biliary cholangitis (PBC) remains unclear. Methods We analyzed the number, phenotypes, and functional molecules of γδ T cells in PBC patients (n = 74) and sex- and age-matched healthy controls (HCs) (n = 74) by flow cytometric analysis. Results We identified two distinct functional subsets of circulating γδ T cells according to the CD3/TCRγδ complex: the TCRγδhigh and TCRγδlow subsets. Approximately three-quarters of cells in the TCRγδhigh subset were Vδ1 T cells, while Vδ2 T cells were enriched in the TCRγδlow subset in HCs. The frequency and absolute number of circulating TCRγδlow cells was significantly decreased in PBC patients compared with HCs (p < 0.001). Furthermore, the frequency of TCRγδlow cells was negatively correlated with disease severity and positively correlated with the ursodeoxycholic acid response. TCRγδlow cells exhibited a similar apoptotic and proliferative phenotype but enhanced liver-homing chemokine receptor (CXCR6) expression in PBC patients compared with HCs. In addition, both TCRγδhigh and TCRγδlow subsets were more activated in PBC compared with HCs, characterized by elevated expression levels of CD69 and HLA-DR. Finally, we found an increased granzyme B (GZMB) production and similar IFN-γ and TNF-α production of TCRγδlow cells in PBC patients compared with HCs. Conclusion The TCRγδlow subset might be a potential marker for disease progression and treatment response in PBC, which may play a crucial role in liver injury through increased CXCR6 expression and GZMB production.